Case report: Genotype-phenotype characteristics of nine novel PKD1 mutations in eight Chinese patients with autosomal dominant polycystic kidney disease

Frontiers in Medicine

Medicine

Yongfang Ren¹  Xiaoqin Wang²  Jun Zhang²  Ailima Aierken²  Jing Zhuang²  Hong Jiang²  Dilina Yalikun²  Xuefei Tian³ 

[1] Department of Radiology and Medical Imaging, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China;Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China;Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States;

关键词: second-generation sequencing;    autosomal dominant polycystic kidney disease;    PKD1;    genotype-phenotype characteristics;    genetic kidney disease;   

DOI  :  10.3389/fmed.2023.1268307

 received in 2023-07-27, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder. The PKD1 gene is responsible for the majority of ADPKD cases, and the mutations in this gene exhibit high genetic diversity. This study aimed to investigate the association between genotype and phenotype in ADPKD patients with PKD1 gene mutations through pedigree analysis.MethodsEight Chinese pedigrees affected by ADPKD were analyzed using whole-exome sequencing (WES) on peripheral blood DNA. The identified variants were validated using Sanger sequencing, and clinical data from the patients and their families were collected and analyzed.ResultsNine novel mutation sites in PKD1 were discovered across the pedigrees, including c.4247T > G, c.3298_3301delGAGT, c.4798A > G, c.7567G > A, c.11717G > C, c.7703 + 5G > C, c.3296G > A, c.8515_8516insG, and c.5524C > A. These mutations were found to be associated with a range of clinical phenotypes, including chronic kidney disease, hypertension, and polycystic liver. The age of onset and disease progression displayed significant heterogeneity among the pedigrees, with some individuals exhibiting early onset and rapid disease progression, while others remained asymptomatic or had milder disease symptoms. Inheritance patterns supported autosomal dominant inheritance, as affected individuals inherited the mutations from affected parents. However, there were instances of individuals carrying the mutations who remained asymptomatic or exhibited milder disease phenotypes.ConclusionThis study highlights the importance of comprehensive genotype analysis in understanding the progression and prognosis of ADPKD. The identification of novel mutation sites expands our knowledge of PKD1 gene mutations. These findings contribute to a better understanding of the disease and may have implications for personalized therapeutic strategies.

【 授权许可】

Unknown   
Copyright © 2023 Zhuang, Aierken, Yalikun, Zhang, Wang, Ren, Tian and Jiang.